Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies from our laboratory demonstrated that N(epsilon)-(carboxymethyl)lysine (CML), one of the major advanced glycation end products (AGE), was accumulated in human pyramidal neurons in the hippocampus in an age-dependent manner. This suggests a potential link between AGE-accumulation and the aging process in neurons. The purpose of the present study was to examine whether this notion could be extended to other AGE structures, such as imidazolone and pentosidine. This was done using 19 human brains that were not affected by dementia. The immunohistochemical survey on distribution in brain tissues of imidazolone and pentosidine was carried out with monoclonal antibodies specific for imidazolone and pentosidine. A parallel control experiment was carried out with anti-CML antibody. The results showed that pentosidine and imidazolone were localized in neurons in different areas of human brain tissue, especially in neurons of CA4 in the hippocampus. The characteristic distribution of pentosidine and imidazolone is very similar to that of CML. Furthermore, when the accumulation of these AGE structures was compared with the age of individual brains it was found that accumulation of imidazolone, pentosidine and CML in the CA4 region increased with age. These findings taken together support the notion that the accumulation of AGE structures in the CA4 region might be closely related to the aging process in neurons.
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PMID:Accumulation of imidazolone, pentosidine and N(epsilon)-(carboxymethyl)lysine in hippocampal CA4 pyramidal neurons of aged human brain. 1240 85

Increasing evidence suggests an interaction of oxidative stress and the formation of advanced glycation end products (AGE) in the onset and progression of Alzheimer's disease. We studied levels of pentosidine and N(epsilon)-(carboxymethyl)-lysine (CML) in serum and cerebrospinal fluid (CSF) of 15 patients with probable Alzheimer's disease (AD), 20 patients with vascular dementia (VD), and 31 control subjects (14 matched for age, and 17 younger patients). AGE protein concentrations in CSF did not differ within controls when divided into two subgroups by age. We found significantly elevated levels of CML in CSF of AD patients and of pentosidine in CSF of patients suffering from vascular dementia when compared to controls. The concentrations of pentosidine and CML in serum apparently did not relate directly to CSF values, suggesting influence of extra-cerebral factors in serum samples. It is concluded that AGE proteins are differentially affected in these types of dementia, depending on the specific neuropathology. Furthermore, measurements of AGE products in vivo should rely on CSF rather than blood samples.
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PMID:Pentosidine and N(epsilon)-(carboxymethyl)-lysine in Alzheimer's disease and vascular dementia. 1249 67

Pick's disease is a subset of fronto-temporal dementia characterised by severe atrophy of the temporal and frontal lobes due to marked neuronal loss accompanied by astrocytic gliosis enriched in glial acidic protein. The remaining neurones have intracytoplasmic inclusions composed of hyperphosphorylated tau, called Pick bodies, in addition to hyperphosphorylated tau in astrocytes and oligodendrocytes. Gel electrophoresis and western blotting using markers of glycoxidation (advanced glycation end products, N-carboxyethyl-lysine and N-carboxymethyl-lysine: AGE, CEL, CML, respectively) and lipoxidation (4-hydroxy-2-nonenal: HNE, and malondialdehyde-lysine: MDAL) were used in the frontal and occipital cortex in three Pick's disease cases and three age-matched controls. In Pick's disease, increased AGE, CML, CEL, HNE and MDAL bands of about 50 kDa were observed in the frontal cortex (but not in the occipital cortex) in association with increased density of glial acidic protein bands. Bi-dimensional gel electrophoresis and western blotting also disclosed increased amounts and numbers of glial acidic protein isoforms in the frontal cortex in Pick's disease. Moreover, redox proteomics showed glycoxidation, as revealed with anti-CEL antibodies and lipoxidation using anti-HNE antibodies, of at least three glial acidic protein isoforms. The present results demonstrate that glial acidic protein is a target of oxidative damage in the frontal cortex in Pick's disease.
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PMID:Glial fibrillary acidic protein is a major target of glycoxidative and lipoxidative damage in Pick's disease. 1698 45